High plasma microfibrillar-associated protein 4 is associated with reduced surgical repair in abdominal aortic aneurysms

Abstract

Objective: Identifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA. Methods: Plasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair. Results: A significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (r ¼ À0.14; P ¼ .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P ¼ .001) for risk of undergoing later surgical repair. Conclusions: High levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.

MFAP4 Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation Through Regulation of Macrophage Infiltration and Activity

“…However, the pattern of MFAP4 regulation has shown inconsistency (47)(48)(49), and a role of MFAP4 in clinical AAA remains unknown. We have recently shown that high plasma MFAP4 is associated with reduced risk of undergoing later surgical repair in AAA (50); however, this observation needs validation in an independent cohort.…”

Development and Validation of a Prognostic Nomogram Based on DNA Methylation-Driven Genes for Patients With Ovarian Cancer

“…Microfibrillar-associated protein 4 (MFAP4), known as 36-kDa microfibril-associated glycoprotein (MAGP36), is ubiquitously distributed in the extracellular matrix of the human body ( Toyoshima et al, 2005 ; Schlosser et al, 2006 ). MFAP4 has been associated with immune response ( Niu et al, 2011 ), liver fibrosis ( Madsen et al, 2020 ), renal fibrosis ( Pan et al, 2020 ), atherosclerosis ( Wulf-Johansson et al, 2013 ), pulmonary airspace enlargement ( Holm et al, 2015 ), and abdominal aortic aneurysms ( Lindholt et al, 2020 ). MFAP4 was also found to be involved in human cancers, such as pancreatic adenocarcinoma ( Guerrero et al, 2021 ), serous OC ( Zhao et al, 2019 ), breast cancer ( Yang et al, 2019 ), and lung cancer ( Feng et al, 2020 ).…”

Patient-derived microphysiological model identifies the therapeutic potential of metformin for thoracic aortic aneurysm

“…Previous studies have shown that upregulation of MFAP4 is a compensatory response to the abnormal elastin formation in Marfan syndrome patients, and lower MFAP4 protein expression in abdominal aortic aneurysm reflects the increased expression of proteases or the loss of contractile vascular smooth muscle cells. 72 , 75 On Day 21, HAoSMCs that underwent rhythmic strain (D21-strain) exhibited enhanced expression of contractile phenotypic marker ACTA2, which was comparable to that in normal aortic tissues. OPN, ELN, MFAP4, TIMP1, and MAPK1 were also comparably expressed on the dynamic microphysiological models and in normal aortic tissues.…”